Chimpanzees experimentally-infected with Mycoplasma pneumoniae developed overt signs of clinical disease which corresponded with the onset of positive X-ray findings, the development of cold agglutinins and peak lung colonization. The immunized chimpanzees became colonized, but did not develop signs of disease and were partially protected. The previously- infected chimpanzees were completely protected against challenge. In the present study, sera from these different groups of chimpanzees were examined by immunoblot and compared in an attempt to identify the protective immunogens. Infected chimpanzee reacted with 17 to 20 protein bands and produced immunoblot patterns remarkably similar to a patient's convalescent sera. Whereas the acellular vaccine induced only a minimal antibody response against three proteins (61, 42 and 30 kDa), the formalin- inactivated vaccine failed to induce any serum immunoblot response. All immunized animals seroconverted after challenge. Although the immunoblot patterns among the three groups were similar, variations were noted among individuals within the same group and between groups. The previously infected chimpanzees who were fully protected on challenge showed the most impressive immunologic responses. The most prominent immunodominant components were the 169 kDa protein band that co-migrated with the well- established P1 adhesin, and protein bands at 117, 86, 35 and 30 kDa. The 86 and 35 kDa polypeptides may represent new and important immunogens because they were present in the pathogenic, cytadsorbing strains PI-1428, M129 and FH, but not the non-pathogenic, non-cytadsorbing strain B176. Thus, the most prominantly recognized immunogenic components of M. pneumoniae following both naturally-occurring disease in patients and experimentally-induced disease in chimpanzees are the 169, 86 and 35 kDa polypeptides. These proteins may also represent the most important immunogens for inclusion in the development of a protective acellular vaccine. A manuscript is being prepared for publication.